Wide Range Near-Zero Thermal Quenching of Orange-Yellow Phosphor via Impeding Self-Oxidation of Eu2+ for Versatile Optoelectronic Applications.

Li2SrSiO4:Eu2+ is a promising substitute for traditional Y3Al5O12:Ce3+ (YAG:Ce3+) owing to its strong orange-yellow emission of 4f-5d transition originating from Eu2+ dopant, covering the more red-light region. However, its inevitable luminescence thermal quenching at high temperatures and the self-oxidation of Eu2+ strongly impede their applications. Their remediation remains highly challenging. Herein, an anti-self-oxidation(ASO) concept of Eu2+ in Li2SrSiO4 substrate by adding trivalent rare-earth ions (A3+: A = La, Gd, Y, Lu) for highly efficient and stable orange-yellow light emission have been proposed. A significantly increased orange-yellow emission (202% improvement) from Li2Sr0.95A0.05SiO4:Eu2+ with a wide range near-zero thermal quenching is obtained, superior to other Eu2+ activated phosphors. The presence of A3+ ions with various radii modifies the ASO degree of Eu2+ ions, achieving the tunable chemical state, composition, electronic configuration, crystal-field strength, and luminescent characteristics of the developed phosphors. For the proof of the concept, a W-LED device and a PDMS (Polydimethylsiloxane) luminescent film are fabricated, endowing excellent luminescence performance and thermal stability and the huge application prospects of Li2SrSiO4:Eu2+ in lighting and display fields.

Quantifying Structural Polarization by Continuous Regulation of Lone-Pair Electron Expression in Molecular Crystals.

Rational design of structural polarization is vital for modern technologies, as it allows the physical properties of functional materials to be tailored. An effective approach for governing polarization involves the utilization of stereochemical lone-pair electrons (LPEs). However, despite the recognized significance of LPEs in controlling structural polarization, there remains a lack of understanding regarding the quantitative relationship between their expression and the extent of structural polarization. Here, by using pressure to continuously tune the LPE expression, we achieve the precise control and quantification of structural polarization, which brings enhanced second harmonic generation (SHG) of the molecular crystal SbI3·3S8. We introduce the I-Sb-I angle (α̅) that describes the degree of LPE expression and establishes a quantitative relationship between α̅ and structural polarization. That is, decreasing α̅ shapes LPE expression from delocalization to localization, which repels the bonding pairs of electrons and thus enhances the structural polarization. In addition, we extend this quantified relationship to a series of molecular crystals and demonstrate its applicability to the design of structural polarization by tailoring LPE expression.

Catalytic Asymmetric Construction of C- and Si-Stereogenic Silacyclopentanes via Hydrosilylation of Arylmethylenecyclopropanes.

Silacycles have exhibited significant potential for application in the fields of medicinal chemistry, agrochemistry, and materials science. Accordingly, the development of effective methods for synthesizing these compounds has attracted increasing attention. Here, we report an efficient Cu-catalyzed enantioselective hydrosilylation of arylmethylenecyclopropanes with hydrosilanes, that allows the rapid assembly of various enantioenriched carbon- and silicon-stereogenic silacyclopentanes in good yields with excellent enantioselectivities and diastereoselectivities under mild conditions. Further stereospecific transformation of the Si-H bond on the chiral silicon center expands the diversity of these C- and Si-stereogenic silacyclopentanes.

Analyzing and identifying predictable time range for stress prediction based on chaos theory and deep learning.

Propose: Stress is a common problem globally. Prediction of stress in advance could help people take effective measures to manage stress before bad consequences occur. Considering the chaotic features of human psychological states, in this study, we integrate deep learning and chaos theory to address the stress prediction problem. Methods: Based on chaos theory, we embed one's seemingly disordered stress sequence into a high dimensional phase space so as to reveal the underlying dynamics and patterns of the stress system, and meanwhile are able to identify the stress predictable time range. We then conduct deep learning with a two-layer (dimension and temporal) attention mechanism to simulate the nonlinear state of the embedded stress sequence for stress prediction. Results: We validate the effectiveness of the proposed method on the public available Tesserae dataset. The experimental results show that the proposed method outperforms the pure deep learning method and Chaos method in both 2-label and 3-label stress prediction. Conclusion: Integrating deep learning and chaos theory for stress prediction is effective, and can improve the prediction accuracy over 2% and 8% more than those of the deep learning and the Chaos method respectively. Implications and further possible improvements are also discussed at the end of the paper.

[Identification of TCTN1 gene variants in a fetus with Joubert syndrome 13].

OBJECTIVE: To explore the clinical characteristics and genetic basis for a fetus with Joubert syndrome. METHODS: A pregnant woman who had visited Suzhou Municipal Hospital on February 26, 2021 was selected as the study subject. The fetus and her parents were subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing. cDNA analysis of her father and RNA sequencing of her sister were also carried out. RESULTS: The fetus was found to harbor compound heterozygous variants of the TCTN1 gene, namely c.624G>A and c.96dupA (p.Glu33Argfs*49), which were inherited from her father and mother, respectively. Her sister also carried the paternal c.624G>A variant, and mRNA transcripts with the c.624G>A variant of the TCTN1 gene were not detected by cDNA analysis of her father and RNA sequencing of her sister. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.624G>A and c.96dupA variants were both classified as likely pathogenic (PVS1+PM2_Supporting). CONCLUSION: The compound heterozygous variants of the TCTN1 gene probably underlay the pathogenesis in this fetus. Above finding has also expanded the mutational spectrum of the TCTN1 gene.

Above-Room-Temperature Ferroelectricity and Giant Second Harmonic Generation in 1D vdW NbOI3.

The realization of spontaneous ferroelectricity down to the one-dimensional (1D) limit is both fundamentally intriguing and practically appealing for high-density ferroelectric and nonlinear photonics. However, the 1D vdW ferroelectric materials are not discovered experimentally yet. Here, the first 1D vdW ferroelectric compound NbOI3 with a high Curie temperature TC > 450 K and giant second harmonic generation (SHG) is reported. The 1D crystalline chain structure of the NbOI3 is revealed by cryo-electron microscopy, whereas the 1D ferroelectric order originated from the Nb displacement along the Nb-O chain (b-axis) is confirmed via obvious electrical and ferroelectric hysteresis loops. Impressively, NbOI3 exhibits a giant SHG susceptibility up to 1572 pm V-1 at a fundamental wavelength of 810 nm, and a further enhanced SHG susceptibility of 5582 pm V-1 under the applied hydrostatic pressure of 2.06 GPa. Combing in situ pressure-dependent X-ray diffraction, Raman spectra measurements, and first-principles calculations, it is demonstrated that the O atoms shift along the Nb─O atomic chain under compression, which can lead to the increased Baur distortion of [NbO2I4] octahedra, and hence induces the enhancement of SHG. This work provides a 1D vdW ferroelectric system for developing novel ferroelectronic and photonic devices.

A novel AI-based diagnostic model for pertussis pneumonia.

It is still very difficult to diagnose pertussis based on a doctor's experience. Our aim is to develop a model based on machine learning algorithms combined with biochemical blood tests to diagnose pertussis. A total of 295 patients with pertussis and 295 patients with non-pertussis lower respiratory infections between January 2022 and January 2023, matched for age and gender ratio, were included in our study. Patients underwent a reverse transcription polymerase chain reaction test for pertussis and other viruses. Univariate logistic regression analysis was used to screen for clinical and blood biochemical features associated with pertussis. The optimal features and 3 machine learning algorithms including K-nearest neighbor, support vector machine, and eXtreme Gradient Boosting (XGBoost) were used to develop diagnostic models. Using univariate logistic regression analysis, 18 out of the 27 features were considered optimal features associated with pertussis The XGBoost model was significantly superior to both the support vector machine model (Delong test, P = .01) and the K-nearest neighbor model (Delong test, P = .01), with the area under the receiver operating characteristic curve of 0.96 and an accuracy of 0.923. Our diagnostic model based on blood biochemical test results at admission and XGBoost algorithm can help doctors effectively diagnose pertussis.

Prebiotic stachyose inhibits PRDX5 activity and castration-resistant prostate cancer development.

Stachyose (STA) is a prebiotic with poor oral bioavailability. In this study, we developed stachyose caproate (C6-STA), as a novel STA derivative, to demonstrate its high adsorption rate via oral administration. Pharmacokinetic analysis reveals that after absorption, the STA derived from C6-STA reaches its highest peak in the blood, liver, and kidney at 20 min, 30 min, and 12-24 h, with approximate levels of 1200 µg/mL, 0.14 µg/mL, and 0.2-0.3 µg/mL, respectively. In addition, the accumulation of STA in prostate tissues of mice with castration-resistant prostate cancer (CRPC) (1.75 µg/mg) is 10-fold higher than that in normal prostate tissues (0.14 µg/mg). The analysis also reveals that C6-STA has t1/2 of 12.8 h and Tmax of 0.25 h, indicating that it has the potential to be used as a promising drug in clinical practice. The toxicological evaluation shows no obvious side effects of C6-STA in mice administered with a 0.2 g/kg intragastric dose. Pharmacodynamic analysis and mechanism investigation of C6-STA show its ability to inhibit peroxiredoxin 5 (PRDX5) enzyme activity, disrupt PRDX5-nuclear factor erythroid 2-related factor 2 (NRF2) interaction, and decrease NAD(P)H quinone dehydrogenase 1 (NQO1) levels. NQO1 decrease further causes the accumulation of quinone radicals, which ultimately leads to the apoptosis of LNCaP cell-derived drug-tolerant persister (DTP) cells and slows CRPC progression. Our study discovered the anti-tumor activity of stachyose and shows that prebiotics have biological functions in vivo besides in the gut. Further investigation of C6-STA, especially in CRPC patients, is warranted.

Grasshopper platform-assisted design optimization of fujian rural earthen buildings considering low-carbon emissions reduction.

This work aims to explore optimization methods for the design of earthen buildings in rural Fujian to achieve low-carbon emissions and improve the structural stability of earthen buildings. First, parametric modeling and optimization algorithms are employed through the Grasshopper platform. An intelligent earthen building design is created by combining the optimization of factors such as the structure of earthen buildings, building materials, and orientation. Then, a comparison is made with the unoptimized, energy-efficient, and carbon emission reduction designs. Finally, the work concludes that the proposed design significantly optimizes the total carbon emissions, energy consumption, structural stability, and economic aspects. The proposed design scheme achieves the highest carbon emission reduction effect, with a reduction rate of 34.64%. The proposed design exhibits lower maximum stress and higher minimum safety factor in terms of structural stability compared to other scenarios, along with smaller structural displacement. It also performs well in terms of initial investment, annual operating costs, and construction period. The significance of this work lies in providing scientific guidance for the design and construction of rural earthen buildings, promoting the organic integration of rural development with low-carbon initiatives. This indicates that the use of intelligent optimization methods for earthen building design is feasible and can yield positive results in practice.

Case report: First Chinese patient with family partial lipodystrophy type 6 due to novel compound heterozygous mutations in the LIPE gene.

Background: Family partial lipodystrophy (FPLD) is a rare autosomal dominant disease characterized by disorders of variable body fat loss associated with metabolic complications. FPLD6 has only been reported in a limited number of cases. Here, we reported a Chinese FPLD6 patient with compound heterozygous mutations in the lipase E, hormone-sensitive type (LIPE) gene. Case presentation: A 20-year-old female patient presented with hypertriglyceridemia, diabetes mellitus, hepatomegaly, and hepatic steatosis. Subcutaneous fat was significantly diminished in her face, abdomen, and limbs. The patient was assessed by detailed clinical and biochemical examinations. A liver biopsy showed severe lipodystrophy. In addition, there were retinal changes, peripheral nerve damage, and renal tubular injury. Sequencing was performed on extracted DNA. Genetic analysis revealed that the patient had compound heterozygous mutations in the LIPE gene: c.2497_250ldel (p.Glu833LysfsTer22) and c.2705del (p.Ser902ThrfsTer27) heterozygous mutations. Verification revealed that this mutation was inherited from her father and mother, respectively, and that they formed newly discovered compound heterozygous mutations occurring in the LIPE gene, causing FPLD6. Conclusion: We reported the first case of FPLD6 in China. Gene analysis demonstrated compound heterozygous mutations in LIPE in this patient. Our case emphasizes the importance of genetic testing in young patients with severe metabolic syndromes.

Hydrogenation of CO2 to formate catalyzed by a Ru catalyst supported on a copolymerized porous organic polymer.

The catalytic hydrogenation of carbon dioxide to formate is of great interest due to its significant role in CO2 utilization. In this study, a novel heterogeneous Ru(III) catalyst was prepared by immobilizing RuCl3 on a porous organic polymer (POP) obtained from 1,4-phthalaldehyde (PTA) and 4,4'-biphenyldicarboxaldehyde (BPDA) with melamine. A copolymerization strategy utilizing monomers of varying lengths was employed to prepare the POP-supported Ru catalyst with adjustable porosity. The optimization of the framework porosity resulted in enhanced CO2 affinity, accelerated mass transfer, and a remarkable enhancement in catalytic activity. A high turnover number (TON) of 2458 was achieved for the CO2 hydrogenation to formate in 2 h with catalyst Cat-3 under 3 MPa (CO2/H2 = 1 : 1) at 120 °C in 1 M Et3N aqueous solution. Moreover, the Cat-3 demonstrated good recyclability and was able to be reused for five consecutive runs, resulting in a high total TON of 9971.

Aging properties of polyethylene and polylactic acid microplastics and their adsorption behavior of Cd(II) and Cr(VI) in aquatic environments.

In this study, we examined the aging characteristics of polyethylene (PE) and polylactic acid (PLA) microplastics (MPs), examining the adsorption behaviors and mechanisms concerning Cd(II) and Cr(VI) under both single and binary systems. The results revealed that aging treatment changed the physicochemical properties of MPs. The aging mechanisms of PLA and PE MPs were shown to be similar by the 2D-FTIR-COS study. These mechanisms involve the formation of oxygen-containing functional groups through the combination of carbon chain breakdown and oxygen. Aged MPs had a greater ability to adsorb metal ions than pristine MPs, with PLA MPs outperforming PE MPs. After 30 days of aging, Cd(II) adsorption increased by 40.61 % and 25.49 % for PE and PLA MPs, respectively, while Cr(VI) adsorption increased by 37.50 % and 69.29 %, respectively. The adsorption ability of PE and PLA MPs with Cd(II) or Cr(VI) under binary systems was less than that under single systems, with Cd(II) exhibiting more adsorption competitiveness than Cr(VI). Humic acid (HA), ionic species and strength, solution pH, and adsorption of Cd(II) and Cr(VI) were found to be significantly correlated. Further investigation into the adsorption mechanisms of Cd(II) and Cr(VI) on PE and PLA MPs revealed that pore-filling, electrostatic interactions, complexation, and hydrogen bonding play important roles in the adsorption process. The study's conclusions are crucial for assessing the risk associated with concurrent contamination by metal ions and microplastics.

Long-Term Efficacy and Safety of Stapokibart in Adults with Moderate-to-Severe Atopic Dermatitis: An Open-Label Extension, Nonrandomized Clinical Trial.

BACKGROUND: Stapokibart/CM310, a humanized monoclonal antibody targeting the interleukin-4 receptor α chain, has shown promising treatment benefits in patients with moderate-to-severe atopic dermatitis in previous phase II clinical trials. OBJECTIVE: We aimed to evaluate the long-term efficacy and safety of stapokibart in adults with moderate-to-severe atopic dermatitis. METHODS: Enrolled patients who previously completed parent trials of stapokibart received a subcutaneous stapokibart 600-mg loading dose, then 300 mg every 2 weeks up to 52 weeks. Efficacy outcomes included the proportions of patients with ≥ 50%/75%/90% improvements from baseline of parent trials in the Eczema Area and Severity Index, Investigator's Global Assessment, and weekly average of the daily Peak Pruritus Numerical Rating Scale. RESULTS: In total, 127 patients were enrolled, and 110 (86.6%) completed the study. At week 52, the Eczema Area and Severity Index-50/75/90 response rates were 96.3%, 87.9%, and 71.0%, respectively. An Investigator's Global Assessment 0/1 with a ≥ 2-point reduction was achieved in 39.3% of patients at week 16, increasing to 58.9% at week 52. The proportions of patients with ≥ 3-point and ≥ 4-point reductions in the weekly average of daily Peak Pruritus Numerical Rating Scale scores were 80.2% and 62.2%, respectively, at week 52. Improvement in patients' quality of life was sustained over a 52-week treatment period. Treatment-emergent adverse events occurred in 88.2% of patients, with an exposure-adjusted event rate of 299.2 events/100 patient-years. Coronavirus disease 2019, upper respiratory tract infection, and conjunctivitis were the most common treatment-emergent adverse events. CONCLUSIONS: Long-term treatment with stapokibart for 52 weeks showed high efficacy and good safety profiles, supporting its use as a continuous long-term treatment option for atopic dermatitis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04893707 (15 May, 2021).

Team interaction behaviors correlates with team creativity among nursing students: Canonical correlation and moderation analyses.

BACKGROUND: Prior studies have indicated team members' interaction behaviors may predict creativity among nursing students. METHODS: This study investigated the correlation between interaction behaviors and creativity, both individual- and team-level, among nursing students. In this cross-sectional quantitative study, data were obtained from self-reported questionnaires. Individual creativity was assessed using the Torrance Tests of Creative Thinking scale; the perceived team interaction behavior and team creativity were assessed using validated instruments. Canonical correlation analysis was conducted to determine the overall correlation between interaction behaviors, and creativity, and the moderating effect of female proportion dominance was also examined. RESULTS: A total of 164 nursing students (84.1% female) arranged into 14 teams were included in this study. Canonical correlation analysis showed a positive correlation between interaction behaviors and creativity (correlation = 0.88). All dimensions of interactive behaviors were positively related to creativity dimensions. A stronger correlation to team creativity (correlation = 1) was found compared to individual creativity (correlation = 0.07). This study demonstrated that individual interactive behaviors including spontaneous communication and helping behavior predicted high team creativity. CONCLUSIONS: This insight may be valuable for nursing education programs seeking to foster creativity and effective teamwork. The potential moderating effect of female proportions on team interaction behaviors and creativity should be investigated further.

Dynamics of the osmotic lysis of mineral protocells and its avoidance at the origins of life.

The osmotic rupture of a cell, its osmotic lysis or cytolysis, is a phenomenon that active biological cell volume regulation mechanisms have evolved in the cell membrane to avoid. How then, at the origin of life, did the first protocells survive prior to such active processes? The pores of alkaline hydrothermal vents in the oceans form natural nanoreactors in which osmosis across a mineral membrane plays a fundamental role. Here, we discuss the dynamics of lysis and its avoidance in an abiotic system without any active mechanisms, reliant upon self-organized behaviour, similar to the first self-organized mineral membranes within which complex chemistry may have begun to evolve into metabolism. We show that such mineral nanoreactors could function as protocells without exploding because their self-organized dynamics have a large regime in parameter space where osmotic lysis does not occur and homeostasis is possible. The beginnings of Darwinian evolution in proto-biochemistry must have involved the survival of protocells that remained within such a safe regime.

[Genetic analysis of a fetus with Rhizomelic skeletal dysplasia].

OBJECTIVE: To explore the clinical features and genetic basis for a fetus featuring Rhizomelic skeletal dysplasia. METHODS: A fetus diagnosed at the Reproductive and Genetic Center of Suzhou Municipal Hospital in November 2020 was selected as the study subject. Whole exome sequencing (WES) was carried out for the fetus and its parents. Candidate variants were verified by Sanger sequencing. Peripheral blood smears of both parents were also examined. RESULTS: The fetus was found to have a small chest and short limbs, which had suggested skeletal dysplasia. Genetic testing revealed that the fetus has harbored compound heterozygous variants of the LBR gene, including a paternally derived c.1687+1G>A and a maternally derived c.1757G>A (p.Arg586His). The blood smear of the father showed Pelger-Huet anomaly with hyposegmentation of neutrophil nuclei, while the neutrophils of the mother appeared to be normal. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP), the c.1757G>A (p.Arg586His) variant was classified as likely pathogenic (PM3_Strong+PM2_Supporting+PP3), and so was the c.1687+1G>A variant (PVS1-Moderate+PM3+PM2-Supporting+PP4). CONCLUSION: The compound heterozygous variants of the LBR gene probably underlay the pathogenesis of skeletal dysplasia in this fetus.

Identification and Validation of a Novel Tertiary Lymphoid Structures-Related Prognostic Gene Signature in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors originating from the digestive system. Tertiary lymphoid structures (TLS), non-lymphoid tissues outside of the lymphoid organs, are closely connected to chronic inflammation and tumorigenesis. However, the detailed relationship between TLS and HCC prognosis remained unclear. In this study, we aimed to construct a TLS-related gene signature for predicting the prognosis of HCC patients. Methods: The Cancer Genome Atlas (TCGA) clinical data from 369 HCC tissues and 50 normal liver tissues were utilized to examine the differential expression of TLS-related genes. Based on least absolute shrinkage and selection operator (LASSO) Cox regression analysis, the prognostic model was constructed using the TCGA cohort and validated in the GSE14520 cohort and International Cancer Genome Consortium (ICGC) cohort. The Kaplan-Meier (KM) and receiver operating characteristic (ROC) curves were employed to validate the predictive ability of the prognostic model. Furthermore, Cox regression analysis was applied to identify whether the TLS score could be employed as an independent prognosis factor. A nomogram was developed to predict the survival probability of HCC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed for TLS-related genes. Genetic mutation analysis, the CIBERSORT algorithm, and single-sample gene set enrichment analysis (ssGSEA) were used to assess the tumor mutation landscape and immune infiltration. Finally, the role of the TLS score in HCC therapy was investigated. Results: Six genes were included in the construction of our prognostic model (CETP, DNASE1L3, PLAC8, SKAP1, C7, and VNN2), and we validated its accuracy. Survival analysis showed that patients in the high-TLS score group had a significantly better overall survival than those in the low-TLS score group. Univariate, multivariate Cox regression analysis and the establishment of a nomogram indicated that the TLS score could independently function as a potential prognostic marker. A significant association between TLS score and immunity was revealed by an analysis of gene alterations and immune cell infiltration. In addition, two subtypes of the TLS score could accurately predict the effectiveness of sorafenib, transcatheter arterial chemoembolization (TACE), and immunotherapy in HCC patients. Conclusion: In this research, we conducted and validated a prognostic model associated with TLS that may be helpful for predicting clinical outcomes and treatment responsiveness for HCC patients.

Association of Mosaic Chromosomal Alterations and Genetic Factors with the Risk of Cirrhosis.

Background and Aims: Age-related mosaic chromosomal alterations (mCAs) detected from genotyping of blood-derived DNA are structural somatic variants that indicate clonal hematopoiesis. This study aimed to investigate whether mCAs contribute to the risk of cirrhosis and modify the effect of a polygenic risk score (PRS) on cirrhosis risk prediction. Methods: mCA call sets of individuals with European ancestry were obtained from the UK Biobank. The PRS was constructed based on 12 susceptible single-nucleotide polymorphisms for cirrhosis. Cox proportional hazard models were applied to evaluate the associations between mCAs and cirrhosis risk. Results: Among 448,645 individuals with a median follow-up of 12.5 years, we identified 2,681 cases of cirrhosis, 1,775 cases of compensated cirrhosis, and 1,706 cases of decompensated cirrhosis. Compared to non-carriers, individuals with copy-neutral loss of heterozygosity mCAs had a significantly increased risk of cirrhosis (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.12-1.81). This risk was higher in patients with expanded cell fractions of mCAs (cell fractions ≥10% vs. cell fractions <10%), especially for the risk of decompensated cirrhosis (HR 2.03 [95% CI 1.09-3.78] vs. 1.14 [0.80-1.64]). In comparison to non-carriers of mCAs with low genetic risk, individuals with expanded copy-neutral loss of heterozygosity and high genetic risk showed the highest cirrhosis risk (HR 5.39 [95% CI 2.41-12.07]). Conclusions: The presence of mCAs is associated with increased susceptibility to cirrhosis risk and could be combined with PRS for personalized cirrhosis risk stratification.

Enhancing oocyte in vitro maturation and quality by melatonin/bilirubin cationic nanoparticles: A promising strategy for assisted reproduction techniques.

In assisted reproduction techniques, oocytes encounter elevated levels of reactive oxygen species (ROS) during in vitro maturation (IVM). Oxidative stress adversely affects oocyte quality, hampering their maturation, growth, and subsequent development. Thus, mitigating excessive ROS to safeguard less viable oocytes during IVM stands as a viable strategy. Numerous antioxidants have been explored for oocyte IVM, yielding considerable effects; however, several aspects, including solubility, stability, and safety, demand attention and resolution. In this study, we developed nanoparticles by self-assembling endogenous bilirubin and melatonin hormone coated with bilirubin-conjugated glycol chitosan (MB@GBn) to alleviate oxidative stress and enhance oocyte maturation. The optimized MB@GBn exhibited a uniform spherical shape, measuring 128 nm in particle size, with a PDI value of 0.1807 and a surface potential of +11.35 mV. The positively charged potential facilitated nanoparticle adherence to the oocyte surface through electrostatic interaction, allowing for functional action. In vitro studies demonstrated that MB@GB significantly enhanced the maturation of compromised oocytes. Further investigation revealed MB@GB's effectiveness in scavenging ROS, reducing intracellular calcium levels, and suppressing mitochondrial polarization. This study not only offers a novel perspective on nano drug delivery systems for biomedical applications but also presents an innovative strategy for enhancing oocyte IVM.

Rapid identification of early infections in febrile patients after CD19 target CAR-T cell therapy for B-cell malignancies.

BACKGROUND: CD19-targeted chimeric antigen receptor T (CAR-T) cell therapy stands out as a revolutionary intervention, exhibiting remarkable remission rates in patients with refractory/relapsed (R/R) B-cell malignancies. However, the potential side effects of therapy, particularly cytokine release syndrome (CRS) and infections, pose significant challenges due to their overlapping clinical features. Promptly distinguishing between CRS and infection post CD19 target CAR-T cell infusion (CTI) remains a clinical dilemma. Our study aimed to analyze the incidence of infections and identify key indicators for early infection detection in febrile patients within 30 days post-CTI for B-cell malignancies. METHODS: In this retrospective cohort study, a cohort of 104 consecutive patients with R/R B-cell malignancies who underwent CAR-T therapy was reviewed. Clinical data including age, gender, CRS, ICANS, treatment history, infection incidence, and treatment responses were collected. Serum biomarkers procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) levels were analyzed using chemiluminescent assays. Statistical analyses employed Pearson's Chi-square test, t-test, Mann-Whitney U-test, Kaplan-Meier survival analysis, Cox proportional hazards regression model, Spearman rank correlation, and receiver operating characteristic (ROC) curve analysis to evaluate diagnostic accuracy and develop predictive models through multivariate logistic regression. RESULTS: In this study, 38 patients (36.5%) experienced infections (30 bacterial, 5 fungal, and 3 viral) within the first 30 days of CAR T-cell infusion. In general, bacterial, fungal, and viral infections were detected at a median of 7, 8, and 9 days, respectively, after CAR T-cell infusion. Prior allogeneic hematopoietic cell transplantation (HCT) was an independent risk factor for infection (Hazard Ratio [HR]: 4.432 [1.262-15.565], P = 0.020). Furthermore, CRS was an independent risk factor for both infection ((HR: 2.903 [1.577-5.345], P < 0.001) and severe infection (9.040 [2.256-36.232], P < 0.001). Serum PCT, IL-6, and CRP were valuable in early infection prediction post-CAR-T therapy, particularly PCT with the highest area under the ROC curve (AUC) of 0.897. A diagnostic model incorporating PCT and CRP demonstrated an AUC of 0.903 with sensitivity and specificity above 83%. For severe infections, a model including CRS severity and PCT showed an exceptional AUC of 0.991 with perfect sensitivity and high specificity. Based on the aforementioned analysis, we proposed a workflow for the rapid identification of early infection during CAR-T cell therapy. CONCLUSIONS: CRS and prior allogeneic HCT are independent infection risk factors post-CTI in febrile B-cell malignancy patients. Our identification of novel models using PCT and CRP for predicting infection, and PCT and CRS for predicting severe infection, offers potential to guide therapeutic decisions and enhance the efficacy of CAR-T cell therapy in the future.